Neuronopathic Gaucher disease patients have shortened life expectancy. Accumulation of lipids substrates and inflammation causes neurodegeneration in neuronopathic Gaucher disease. Mutations in GBA1, the gene responsible for Gaucher disease, are the most common known genetic risk factors for Parkinson's disease. There are no FDA or EMA-approved therapeutic for neuronopathic Gaucher disease and Parkinson's disease currently available, representing unmet medical needs.
GCase is a druggable target for chaperon therapy. Small molecule pharmaceutical chaperone can be made into an oral drug which can penetrate to the brain and restore mutant GCase. Improved GCase activity by chaperone in brain cells will reduce substrate accumulation, inflammation, mitigate alpha-synuclein pathology and improve sensorimotor and cognitive function. The novel non-inhibitory pharmaceutical chaperons will meet pressing needs for neuronopathic Gaucher disease, it is expected that the benefit of this chaperone therapy will apply to Parkinson's disease.
Conventional enzyme replacement therapy with pharmacologic GCase has been a modestly successful treatment in visceral type Gaucher disease. Because GCase is a very unstable enzyme, patients have to be administrated by intravenous infusion very frequently to maintain therapeutic efficacy. The chaperone stabilizes GCase allowing prolonged drug efficacy. This provides a commercial opportunity to improve current enzyme replacement therapy for visceral forms of Gaucher disease, for example, and reduce the burden on the patients.